A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines

Chay, Christopher H.; Cooper, Carlton R.; Gendernalik, James D.; Dhanasekaran, Saravana M.; Chinnaiyan, Arul M.; Rubin, Mark A.; Schmaier, Alvin H.; Pienta, Kenneth J.

doi:10.1016/s0090-4295(02)01969-6

Cited by 92 publications

(77 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further study indicated PAR-1 was both required and sufficient to promote growth and invasion of breast carcinoma cells in a xenograft model (17). Similar conclusion was also reached in human prostate cancer (11,18,19). In human colon cancer cells, aberrant expression and activation of PAR-1 could induce cell proliferation, matrix adhesion, motility and migration (12,20).…”

Section: Introductionmentioning

confidence: 55%

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

et al. 2012

View full text Add to dashboard Cite

Abstract. Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein, which is involved in physiological and malignant invasion processes. It is activated by serine proteases such as thrombin through a unique form or by specific synthetic peptides. In this study, we determined the expression of PAR-1 in five nasopharyngeal carcinoma (NPC) cell lines with different characteristics of invasiveness and metastasis, and found that the levels of PAR-1 expression were higher in invasive or metastatic cell lines than those in low invasive or metastatic ones. Of the five NPC cell lines, CNE1-LMP1 cells had the highest expression levels of PAR-1, which was mainly distributed at the membrane and in the cytoplasm of tumor cells. Further study showed that the thrombin receptor synthetic activating peptide SFLLRN could stimulate the growth of CNE1-LMP1 cells in a dosedependent manner. However, thrombin itself had a dual effect on the proliferation of NPC cells. Concentrations of thrombin in the range of 0.1-0.5 U/ml promoted cell growth, but concentrations higher than 0.5 U/ml impaired cell growth. Moreover, thrombin and SFLLRN also enhanced the invasive capabilities of CNE1-LMP1 cells in vitro, and this was partly due to enhancing the activities of MMP-2 and MMP-9. Our findings suggest that PAR-1 may contribute to the growth and invasive potential of NPC cells.

show abstract

Section: Introductionmentioning

confidence: 55%

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Proteaseactivated receptor-1, PAR1, the first and prototype member of a PAR family, is emerging as having a central function in tumor progression. We, and others, have shown pro-angiogenic, pro-survival and proinvasive properties of PAR1 (Even-Ram et al, 1998;Chay et al, 2002;Darmoul et al, 2003;Yin et al, 2003;Caunt et al, 2006;Salah et al, 2007a).…”

Section: Introductionmentioning

confidence: 64%

p53 controls hPar1 function and expression

Salah

Haupt²,

Maoz

et al. 2008

Oncogene

View full text Add to dashboard Cite

Human protease-activated receptor 1 (hPar1) is a bona fide receptor of the hemostatic protease thrombin, and has a central function in tumor progression. Inactivation of the tumor suppressor gene p53 is one of the most common genomic alterations occurring in cancer. Here, we address the interrelations between p53 and hPar1 in cancer. We demonstrate an inverse correlation between hPar1 gene expression and wild-type (wt) p53 levels, and a direct correlation with levels of the mutant (mt) p53. Bioinformatic search revealed the presence of at least two p53 motifs in the hPar1 promoter. Indeed, temperaturesensitive (ts) p53 forms reduced hPar1 promoter activity on wt p53 expression. Ectopic introduction of the p53R175H mutant into cells lacking p53 caused a moderate two-fold induction of hPar1 promoter activity. Chromatin immunoprecipitation (ChIP) analyses confirmed a physical association between the p53 protein and hPar1 chromatin fragments. In parallel, PAR1 function is attenuated by p53, as shown by inhibition of pFAK levels and a Matrigel invasion assay. Ectopic reinforcement of hPar1 rescued the inhibition conferred by p53, confirming that p53 directly affects hPar1 expression and function. Altogether, we provide evidence for a direct binding between p53 and hPar1 chromatin, and assign hPar1 as a target of p53.

show abstract

“…Basic and clinical research results demonstrate that GPCR systems in some advanced prostate cancers may be excessively activated, due to abnormally elevated ligands of GPCRs (Nelson et al, 1996;Porter and BenJosef, 2001;Xie et al, 2002) and/or overexpression of GPCRs including endothelin A receptor (Gohji et al, 2001), bradykinin 1 receptor (Taub et al, 2003), folliclestimulating hormone receptor (Ben-Josef et al, 1999), thrombin receptor (Chay et al, 2002) and the orphan prostate-specific GPCR (Xu et al, 2000;Xia et al, 2001;Weng et al, 2005). In addition, advanced prostate cancers often have increased numbers of neuroendocrine cells that are known to secrete neuropeptides (Abrahamsson, 1999).…”

Section: Introductionmentioning

confidence: 99%

Regulator of G-protein signaling 2 (RGS2) inhibits androgen-independent activation of androgen receptor in prostate cancer cells

et al. 2006

View full text Add to dashboard Cite

Expression of RGS2, but not other RGS proteins, abolished androgen-independent AR activity in androgenindependent LNCaP cells and CWR22Rv1 cells. In LNCaP cells, RGS2 inhibited G q -coupled GPCR signaling. Expression of exogenous wild-type RGS2, but not its GAP-deficient mutant, significantly reduced AR activation by constitutively activated G q Q209L mutant whereas silencing endogenous RGS2 by siRNA enhanced G q Q209L-stimulated AR activity. RGS2 had no effect on RGS-insensitive G q Q209L/G188S-induced AR activation. Furthermore, extracellular signal-regulated kinase 1/2 (ERK1/2) was found to be involved in RGS2-mediated regulation of androgen-independent AR activity. In addition, RGS2 functioned as a growth suppressor for androgen-independent LNCaP cells whereas androgensensitive LNCaP cells with RGS2 silencing had a growth advantage under steroid-reduced conditions. Finally, RGS2 expression level was significantly decreased in human prostate tumor specimens. Taken together, our results suggest RGS2 as a novel regulator of AR signaling and its repression may be an important step during prostate tumorigenesis and progression.

show abstract

A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines

Cited by 92 publications

References 10 publications

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

p53 controls hPar1 function and expression

Regulator of G-protein signaling 2 (RGS2) inhibits androgen-independent activation of androgen receptor in prostate cancer cells

Contact Info

Product

Resources

About